The long-term goal of this project is to elucidate the physiological effects of 5-hydroxytryptamine (5-HT, serotonin) in the hippocampus, establish the cellular mechanism(s) responsible for these effects, and characterize the 5-HT receptor(s) associated with them using the hippocampal slice preparation In Vitro. One objective for the present project period is to define the effects of 5-HT on extracellular field potentials in the three major areas of the hippocampal slice, CA1, CA3, and the dentate gyrus. Within each area, field potentials will be recorded from the cell body layer and the dendritic layer. A second objective is to generate dose-response curves for 5-HT from all three areas of the hippocampus. These experiments will reveal the sensitivity of the receptor in the three hippocampal areas, which have been shown by radioautographic methods to differ in 5-HT binding site density. The third objective is to characterize the 5-HT receptor(s) associated with the electrophysiological responses. Towards this end, 5-HT agonsits (e.g., tryptamine, 5-methoxytryptamine) and antagonists (e.g., LSD, BOL, methysergide, Ketanserin, spiroperidol) will be tested on the system. For agonists, complete dose-response curves will be done, from which will be calculated EC-50 values (the concentration to produce 50% of the maximal response). For antagonists, the experiments are designed to obtain dissociation constants, KD values. These values and the rank orders of potencies will be compared to those obtained, in this and other laboratories, on hippocampal 5-HT receptors by binding studies and by studies of the 5-HT stimulated adenylate cyclase. The work on extracellular field potentials will provide a groundwork for future electrophysiological studies in which intracellular recordings will be used to study the mechanism(s) of the 5-HT effect(s).